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胎儿神经元向边缘皮质的早期定向分化。

The early commitment of fetal neurons to the limbic cortex.

作者信息

Barbe M F, Levitt P

机构信息

Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129.

出版信息

J Neurosci. 1991 Feb;11(2):519-33. doi: 10.1523/JNEUROSCI.11-02-00519.1991.

Abstract

The limbic-system-associated membrane protein (LAMP) is expressed early in cerebral cortical development by migrating and postmigratory neurons in limbic regions such as the prefrontal and perirhinal cortices (Horton and Levitt, 1988), but not by nonlimbic neurons such as in the primary sensory and motor cortices. In the present study, we used LAMP expression to evaluate the timing and potential cell-lineage and environmental determinants of the commitment of cerebral cortical neurons to limbic and nonlimbic phenotypes. The cerebral wall, containing either presumptive perirhinal or sensorimotor cortex, was removed prior to [embryonic day (E) 12, 14] or just after (E17) the onset of LAMP expression, labeled with fast blue, and placed into cavities in either perirhinal or sensorimotor regions of postnatal day (P) 1 hosts. Host animals were allowed to survive until at least P10, and surviving transplanted cells were counted and evaluated for LAMP expression. Sensorimotor cortical neurons transplanted at E14 or E17, in either homotopic or heterotopic locations, did not express LAMP. In contrast, a high percentage of perirhinal cortical neurons transplanted at either E14 or E17, whether situated in sensorimotor or perirhinal regions of the host, expressed the limbic marker protein. Surprisingly, neurons from E12 donors exhibited patterns of LAMP expression that reflected their new location in the host rather than their embryonic origin. The data suggest that there is an early pliant period in which precursor and early differentiating cells remain uncommitted to a particular cortical regional phenotype. After this period, one aspect of the molecular phenotype (determined by LAMP expression) of neurons destined for sensorimotor and allo- and mesocortical regions has become immutable by environmental factors in the host.

摘要

边缘系统相关膜蛋白(LAMP)在大脑皮质发育早期由迁移和迁移后的神经元在前额叶和嗅周皮质等边缘区域表达(霍顿和莱维特,1988年),但在初级感觉和运动皮质等非边缘神经元中不表达。在本研究中,我们利用LAMP表达来评估大脑皮质神经元向边缘和非边缘表型分化的时间、潜在细胞谱系和环境决定因素。在LAMP表达开始前(胚胎第12、14天)或之后(第17天),取出含有假定的嗅周皮质或感觉运动皮质的脑壁,用快蓝标记,然后放入出生后第1天宿主的嗅周或感觉运动区域的腔中。让宿主动物存活至至少第10天,对存活的移植细胞进行计数并评估LAMP表达情况。在第14天或第17天移植的感觉运动皮质神经元,无论在同位还是异位位置,均不表达LAMP。相比之下,在第14天或第17天移植的嗅周皮质神经元,无论位于宿主的感觉运动区域还是嗅周区域,有很大比例表达边缘标记蛋白。令人惊讶的是,来自第12天供体的神经元表现出的LAMP表达模式反映了它们在宿主中的新位置,而非其胚胎起源。数据表明,存在一个早期可塑性时期,在此期间前体细胞和早期分化细胞尚未确定为特定的皮质区域表型。在此时期之后,注定要进入感觉运动区域以及同型和中间皮质区域的神经元分子表型的一个方面(由LAMP表达决定)已因宿主环境因素而变得不可改变。

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